ALLOGENEIC DENDRITIC CELL INDUCTION OF HIV-SPECIFIC CYTOTOXIC T-LYMPHOCYTE RESPONSES FROM T-CELLS OF HIV TYPE 1-INFECTED AND UNINFECTED INDIVIDUALS

The potential benefit of T cell-based vaccination for HIV-1 infection remains to be determined. Cytotoxic T lymphocytes (CTLs) appear to cle ar substantial populations of HIV-1 virus in vivo, although CTL activi ty may contribute to the decline in CD4(+) T cell count observed in th e course of disease. To investigate further the role of specific CTL r esponses in the control of HIV-1 replication, we raised primary CTL li nes against a panel of conserved HIV-1 epitopes using blood-derived de ndritic cells as antigen-presenting cells (APCs), Specific primary hum an CTL responses were induced against HLA-A0201-restricted peptides w ith dendritic cells from HIV-l-seronegative donors. This method of imm unization elicited cytotoxic activities capable of recognizing endogen ously processed antigen. The CTL induction protocol was extended in or der to explore the capacity of HLA-matched allogeneic dendritic cells to evoke novel CTL responses in T cells from an HIV-seropositive asymp tomatic individual. Allogeneic peptide-pulsed dendritic cells from a h ealthy sibling were capable of eliciting a CTL response directed again st an HIV epitope (env814: SLLNATDIAV) that was initially not detected in the CTL effector population of the HIV-1-infected patient, The pos sibility of manipulating CTL specificity directed against multiple con served HIV-1 epitopes represents a significant step in the evaluation of T cell-based vaccination for treatment of disease.